The present invention relates to a system (method and apparatus) for cellular surgery utilizing confocal microscopy, and relates particularly to, a system for cellular surgery which provides for confocal imaging of tissue and treatment of one or more cells of the tissue being imaged. Cellular surgery is herein defined as surface or subsurface excision, ablation, thermolysis, photo-drug activation, or photo-chemical or photo-acoustical changes, on a region of tissue characterized by one or more individual cells.
Confocal microscopy involves scanning tissue to produce microscopic sectional images of surface or subsurface tissue. Such microscopic imaged sections may be made in-vivo and can image at cellular resolutions. Examples of confocal scanning microscopes are found in U.S. Pat. No. 5,788,639, issued Aug. 4, 1998 to James M. Zavislan, and in Milind Rajadhyaksha et al., xe2x80x9cIn vivo Confocal Scanning Laser Microscopy of Human Skin: Melanin provides strong contrast,xe2x80x9d The Journal of Investigative Dermatology, Volume 104, No. 6, June 1995, pages 1-7. For further information concerning the system of the Zavislan application, see Milind Rajadhyaksha and James M. Zavislan, xe2x80x9cConfocal laser microscope images tissue in vivo,xe2x80x9d Laser Focus World, February 1997, pages 119-127. These systems have confocal optics which direct light to the patient""s tissue and image the returned reflected light. These confocal systems although useful for examination of lesions or other diseased tissue have no capability for treatment of cells, such as, for example, to cause thermolysis, photolysis, or ablation of imaged cells.
An optical microscope apparatus has been proposed for targeting a laser beam to a cell, as described in U.S. Pat. No. 4,289,378, which utilizes a visible marker laser beam and a non-visible working laser beam focused to different spots of a cell of an in-vitro sample. This device however does not use confocal microscopy for tissue imaging and does not provide treatment of cells of in-vivo tissue of a patient.
A microsurgical instrument with electronic visualization of tissue being treated is described in U.S. Pat. No. 5,653,706, in which energy from a single laser is applied to selected locations under skin to provided localized photothermolysis of tissue at such locations. Visualization of the tissue is provided by a CCD video camera in the instrument. Confocal microscopy is not utilized for tissue imaging.
Accordingly, the principal object of the present invention is to provide an improved system for generating confocal images of in-vivo tissue which enables surgical treatment of tissue being imaged.
A further object of the present invention is to provide an improved system for generating confocal images of in-vivo tissue which enables surgical treatment either to be localized to a small region of tissue being imaged, or to be non-localized over a region of tissue including that small region of tissue.
Another object of the present invention is to provide an improved system for generating through confocal optics images of in-vivo tissue which enables laser surgical treatment of the tissue being imaged, allows for evaluating the effectiveness of such treatment by simultaneously or sequentially imaging the treated tissue, and for modifying the operating parameters of the laser and/or confocal optics in subsequent treatments of the tissue.
Briefly described, the present invention embodies a system including a laser for producing a laser beam, and confocal optics for scanning and focusing the beam in tissue and collecting returned light from the tissue. A detector is provided which confocally detects the returned light and produces signals in accordance with the detected returned light representing confocal images. Responsive to the signals, such confocal images are visualized on a display. The system further includes a programmed controller for enabling the operator to select one or more cells of the tissue in the visualized confocal images for surgical treatment. The controller operates the laser and confocal optics in a first mode at a first set of operating parameters to treat the tissue when the confocal optics focus the laser beam at least one region associated with the selected cells in the tissue, but at all other times operates the laser and confocal optics in a second mode at a second set of operating parameters which does not damage the tissue.
The region may include at least one of the selected cells and other cells of the tissue surrounding the selected cell, thereby providing non-localized treatment. The region may also be localized to at least one of said selected cells, thereby providing localized treatment.
The above operating parameters may include the energy density, pulse width, duty cycle, power, or wavelength of the laser, and the scan rate, field of view, or depth of focus provided by the confocal optics. At the first set of operating parameters sufficient laser energy exposure is provided to the tissue to effect treatment of the tissue. All or some of the operating parameters may differ between the first and second sets of operating parameters.
The present invention also embodies an apparatus having a confocal imaging system which focuses a first laser beam through confocal optics to tissue and provides confocal images of the tissue. A treatment system is provided which focuses a second laser beam through the confocal optics coaxial with the first laser beam for treating one or more selected locations in the imaged tissue.